Neural tone and cardio-renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus
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Neural tone and cardio‑renal outcomes in patients with type 2 diabetes mellitus: a review of the literature with a focus on SGLT2 inhibitors Mouhamed Nashawi1 · Omar Sheikh1 · Ayman Battisha2 · Abdullah Ghali1 · Robert Chilton1 Accepted: 19 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Recent clinical trials involving the systemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have revealed beneficial outcomes pertaining to the microvascular sequelae of type 2 diabetes mellitus (T2DM) such as nephropathy, as well as macrovascular effects such as major adverse cardiovascular effects (MACE). Such findings have spurred the elevation of these agents to level A-tiers of recommendation within clinical guidelines addressing the management of complicated T2DM. While the mechanisms of SGLTi (-flozin drugs) are still being elucidated, a paucity of data exists within the literature appraising the role of neuromodulation and associated mechanisms in the aforementioned outcome studies. Given the role of the nervous system in orchestrating the pathologic processes that hamper cardio-renal status, insight into this topic offers an expanded perspective on T2DM. In this review we investigate the mechanisms by which SGLTi improve cardio-renal function in T2DM patients with emphases on neural tone and nervous system physiology. Keywords SGLT2 · Diabetes · Neural · Sympathetic · Autonomic · Cardiovascular · Inhibitors · Dapagliflozin · Empagliflozin · Canagliflozin
Background Type 2 diabetes mellitus (T2DM) confers an elevated risk for chronic kidney disease (CKD), with over 40% of cases attributed to diabetes and estimations that roughly one-third of diabetics have CKD per the Centers for Disease Control and Prevention (CDC)[1]. One method of monitoring CKD severity and morbidity is through the measurement of estimated glomerular filtration rate (eGFR). Within the USA, the prevalence of reduced eGFR trended upwards from 9.2% (95%CI, 6.2–12.2%) in the timespan between 1988 and 1994 to a value of 14.1% (95%CI, 11.3–17.0%) between 2009 and 2014, indicating a relative increase of 61% (adjusted prevalence ratio, 1.61 (95%CI) 1.33–1.95)[2]. Moreover, T2DM
* Mouhamed Nashawi [email protected] 1
Division of Medicine‑Cardiology, UT Health San Antonio, 7872, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Department of Internal Medicine, University of Massachusetts Medical School-Bay State, 759 Chestnut Street, Springfield, MA 01199, USA
2
is a significant risk factor for cardiovascular disease (CVD) and is believed to be culpable in at least 50% of CVDrelated deaths while afflicting nearly one-third of patients with CVD[3]. Straka et al. studied 29,863 patients (5501 diagnosed with T2DM and 24,632 without) and found that patients with T2DM exhibited statistically significant mortality profiles relative to patients without T2DM, with relative risks of 1.10, 1.53, 1.58, and 2.12 for coronary artery disease (CAD), myocardial infarction (MI), stroke, and hear
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